Flavin-containing monooxygenase 3

Flavin-containing monooxygenase 3 (FMO3), also known as dimethylaniline monooxygenase [N-oxide-forming] 3 and trimethylamine monooxygenase, is a flavoprotein enzyme that in humans is encoded by the FMO3 gene. This enzyme catalyzes the following chemical reaction, among others:


 * trimethylamine + NADPH + H+ + O2 $$\rightleftharpoons$$ trimethylamine N-oxide + NADP+ + H2O

FMO3 is the main flavin-containing monooxygenase isoenzyme that is expressed in the liver of adult humans. The human FMO3 enzyme catalyzes several types of reactions, including: the N-oxygenation of primary, secondary, and tertiary amines; the S-oxygenation of nucleophilic sulfur-containing compounds;  and the 6-methylhydroxylation of the anti-cancer agent dimethylxanthenone acetic acid (DMXAA).

FMO3 is the primary enzyme in humans which catalyzes the N-oxidation of trimethylamine into trimethylamine N-oxide; FMO1 also does this, but to a much lesser extent than FMO3. Genetic deficiencies of the FMO3 enzyme cause primary trimethylaminuria, also known as "fish odor syndrome". FMO3 is also involved in the metabolism of many xenobiotics (i.e., exogenous compounds which are not normally present in the body), such as the oxidative deamination of amphetamine. Table 5: N-containing drugs and xenobiotics oxygenated by FMO Table 6: S-containing drugs and xenobiotics oxygenated by FMO Table 7: FMO activities not involving S- or N-oxygenation

Cancer
The FMO3 gene has been observed progressively downregulated in human papillomavirus-positive neoplastic keratinocytes derived from uterine cervical preneoplastic lesions at different levels of malignancy. For this reason, FMO3 is likely to be associated with tumorigenesis and may be a potential prognostic marker for progression of uterine cervical preneoplastic lesions.